To understand the neurocognitive mechanism underlying food-related motivation and control in patients with narcolepsy with cataplexy.
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We will assess the difference in performance (i.e. error rates and reaction
times) and brain activity (using fMRI) in prefrontal cortex control (i.e.
attentional bias to food-related words), and striatum (i.e. food and monetary
reward cue responses).
Secondary outcome
NA
Background summary
Narcolepsy with cataplexy (NC) is caused by hypocretin deficiency. Patients
with this disorder suffer from chronic daytime sleepiness and cataplexy (i.e. a
sudden and transient episode of loss of muscle tone). The hypocretin system is
crucial for arousal and maintenance of the wakening state. Recently, hypocretin
has also been shown to play an important role in reward and motivation.
Hypocretin enhances dopamine signalling in the meso-limbic pathway that
regulates reward processing and addiction. Animal studies have shown that when
hypocretin is blocked in the meso-limbic pathway, addicted animals will stop
drug-seeking behaviour. Furthermore, the meso-limbic pathway and its
interaction with hypocretin has also shown to be important in regulating
food-related motivation in rodents. There is clinical evidence that NC
patients, who are lacking hypocretin, suffer from decreased general motivation
and interestingly; despite the fact that narcoleptic patients are usually
treated with amphetamine-like compounds they rarely develop drug dependency to
their medication. Paradoxically, NC is associated with a global increased
frequency of obesity and higher prevalence of eating disorders. Obesity is
associated with an enhanced food-related motivation and diminished prefrontal
control over food intake. What neuromechanisms contribute to abnormal
food-related motivation and control in NC patients has not yet been studied.
This study will test the neurocognitive mechanisms related to the disturbed
food-related motivation and control in NC by using behavioural and functional
magnetic resonance imaging (fMRI) tasks.
Study objective
To understand the neurocognitive mechanism underlying food-related motivation
and control in patients with narcolepsy with cataplexy.
Study design
We will use a cross sectional, patient-controlled design using a behavioral
task and functional MRI experiments.
Study burden and risks
Both the patients groups will have to refrain from taking their medication
(which usually consists of modafinil or methylphenidate). The severity of the
sleep disorder will range considerable from mild; patients who do not need to
take medication (use planned naps), to severe; with diminished functioning and
in need of the maximum dosage of medication. In consultation with a treating
physician, we expect that when patients are without medication, they will
temporally experience the surfacing of their symptoms (such as sleepiness).
After 1 week, the medication will directly relief the surfaced symptoms as it
did previously (or work even better because of relieving tolerance effects),
without any incubation time. The patient will make the decision whether he or
she wants to go without medication for 1 week. We expect to mostly recruit less
severe patients. On the day preceding each test day, subjects will have to
adhere to some simple restrictions with respect to alcohol and drug intake.
Also, subjects will also have to refrain from smoking on the test day itself,
and from eating anything 5h before the appointment. Subjects will come to the
lab for a test day which will take 3 hours.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age: 18-60 years old
- Right-handed
Control group:
- No current sleep, neurological or psychiatric disorder
Patient groups:
- Narcolepsy with cataplexy, or narcolepsy without cataplexy or idiopathic hypersomnia (without long sleep time). All disorders should have been diagnosed according to the ICSD-2 criteria.
- All patients who take medications should be willing to withdraw from taking medication for 1 week.
Exclusion criteria
- Diabetes Mellitus
- (History of) clinically significant hepatic, cardiac, renal, cerebrovascular, endocrine, metabolic or pulmonary disease
- Uncontrolled hypertension, defined as diastolic blood pressure at rest > 90 mmHg or systolic blood pressure at rest > 160 mmHg
- (History of) clinically significant neurological or psychiatric disorders, and current psychological treatment other than narcolepsy (with/without cataplexy).
- Deafness, blindness, or sensori-motor handicaps
- History of taste or smell impairments
- Drug, alcohol or gamble addiction in the past 6 months
- Inadequate command of Dutch language
- Extreme restraint eating (i.e. score restraint eating >=3.60 (females) or >= 4.00 (males) on the Dutch Eating Behavior Questionnaire; see also section 6.3.4)
- Current, strict dieting (i.e. specific diet and/or in treatment with dietitian)
- Food allergy to one of the ingredients used in the food rewards
- Contra-indications for MRI:
o Metal objects or fragments in the body that cannot be taken out
o Active implants in the body
o Using medical plasters
o Epilepsy
o Previous head surgery
o Pregnancy
o Claustrophobia
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL45550.091.13 |
| OMON | NL-OMON27831 |